Previous work from this laboratory has demonstrated that hyperphenylalaninemia in infant rats produces a brain-specific inhibition of protein synthesis. This is an instructive model for the investigation of aminoacidopathies which result in enduring learning deficits. We propose to continue this study in an effort to further delineate the nature of the defect in brain development. Studies of in vivo brain protein and RNA synthesis during acute hyperphenylalaninemia will attempt to identify proteins with particular susceptibility to phenylalanine effects. Protein phosphorylation will also be investigated with particular reference to its role in polyribosome formation, which we have previously found to be defective following phenylalamine injection. We will attempt to determine if the "Enduring PKU model" is characterized by long-term changes in brain protein composition and we will attempt to prevent brain damage in hyperphenylalaninemia by the administration of agents which promote polyribosome aggregation or prevent amino acid depletion. We will further define the age at which the developing rat brain is no longer vulnerable to the effects of hyperphenylalaninemia, in an attempt to develop landmarks which may prove to be clinically useful.